Alzheimer's disease

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Alzheimer's disease

(ăls`hī'mərz, ôls–), degenerative disease of nerve cells in the cerebral cortex that leads to atrophy of the brain and senile dementia and, ultimately, death. The disease is characterized by abnormal accumulation of plaques and by neurofibrillary tangles (malformed nerve cells), changes in brain tissue first described by Alois Alzheimer in 1906. The plaques result from the release and accumulation of excessive amounts of amyloid-beta (or beta-amyloid) proteins, normal proteins whose function in the body is not known. The neurofibrillary tangles prevent transportation of synthesized products within the cell body to organelles and target sites. The plaques and neurofibrillary tangles prevent proper transmission of electrochemical signals necessary for information processing and retrieval. The plaques also suffocate neurons by inhibiting proper blood supplies from reaching them.

Alzheimer's disease usually affects people over age 65, although it can appear in people as young as 40, especially in some familial forms of the disease. A condition called mild cognitive impairment, in which a person experiences an inability to form memories for events that occurred a few minutes ago, typically is the first sign of the disease. Although other conditions may cause mild cognitive impairment, if no identifiable cause is present, it leads to Alzheimer's in some 80% of the cases. As the disease progresses, a variety of symptoms may become apparent, including loss of memory, anxiety, confusion, irritability, and restlessness, as well as disorientation, impaired judgment and concentration, and more severe emotional and behavioral disorders. Alzheimer's patients ultimately become incapable of properly caring for themselves and communicating, and may become bedridden before dying from the physical effects of the disease (such as the inability to swallow). As an underlying cause of death, the disease is almost as significant as heart disease and cancer, and death rates from Alzheimer's have steadily increased in the early 21st cent.

The cause of Alzheimer's is unknown, but a number of genes appear to be associated with the disease. Mutations in a gene on chromosome 21, which is also associated with Down syndromeDown syndrome,
congenital disorder characterized by mild to severe mental retardation, slow physical development, and characteristic physical features. Down syndrome affects about 1 in every 730 live births and occurs in all populations equally.
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, and another gene on chromosome 14 have been found in early-onset cases. Late-onset cases, which are the vast majority, may be caused by a combination of genetic and environmental factors. In 1999 scientists discovered an enzyme, named beta-secretase, that begins the process in the brain leading to Alzheimer's disease. One study has suggested that the buildup of amyloid-beta protein in some patients is due to slower than normal clearance of the protein from the brain.

There is as yet no known cure. Genetic screening for families with a history of early Alzheimer's is sometimes advised. Treatment includes relieving the patient's symptoms and alleviating stress on caregivers through support groups and counseling services. Donepezil (Aricept), rivastigmine (Exelon), and other acetylcholinesterase inhibitors provide temporary improvement for some patients with mild to moderate Alzheimer's. Memantine (Namenda), which appears to protect against damage from the effects of excess glutamate, slows the progression of the disease in some patients in the late stage of Alzheimer's.

Bibliography

See study by D. Shenk (2001).

Alzheimer's disease

A disease of the nervous system characterized by a progressive dementia that leads to profound impairment in cognition and behavior. Dementia occurs in a number of brain diseases where the impairment in cognitive abilities represents a decline from prior levels of function and interferes with the ability to perform routine daily activities (for example, balancing a checkbook or remembering appointments). Alzheimer's disease is the most common form of dementia, affecting 5% of individuals over age 65. The onset of the dementia typically occurs in middle to late life, and the prevalence of the illness increases with advancing age to include 25–35% of individuals over age 85.

Memory loss, including difficulty in remembering recent events and learning new information, is typically the earliest clinical feature of Alzheimer's disease. As the illness progresses, memory of remote events and overlearned information (for example, date and place of birth) declines together with other cognitive abilities. In the later stages of Alzheimer's disease, there is increasing loss of cognitive function to the point where the individual is bedridden and requires full-time assistance with basic living skills (for example, eating and bathing). Behavioral disturbances that can accompany Alzheimer's disease include agitation, aggression, depressive mood, sleep disorder, and anxiety. See Memory

The major neuropathological features of Alzheimer's disease include the presence of senile plaques, neurofibrillary tangles, and neuronal cell loss. Although the regional distribution of brain pathology varies among individuals, the areas commonly affected include the association cortical and limbic regions.

Deficits in cholinergic, serotonergic, noradrenergic, and peptidergic (for example, somatostatin) neurotransmitters have been demonstrated. Dysfunction of the cholinergic neurotransmitter system has been specifically implicated in the early occurrence of memory impairment in Alzheimer's disease, and it has been a target in the development of potential therapeutic agents. See Acetylcholine, Neurobiology, Noradrenergic system

A definite diagnosis of Alzheimer's disease is made only by direct examination of brain tissue obtained at autopsy or by biopsy to determine the presence of senile plaques and neurofibrillary tangles. A clinical evaluation, however, can provide a correct diagnosis in more than 80% of cases. The clinical diagnosis of Alzheimer's disease requires a thorough evaluation to exclude all other medical, neurological, and psychiatric causes of the observed decline in memory and other cognitive abilities.

Although the cause of Alzheimer's disease is unknown, a number of factors that increase the risk of developing this form of dementia have been identified. Age is the most prominent risk factor, with the prevalence of the illness increasing twofold for each decade of life after age 60. Research in molecular genetics has shown that Alzheimer's disease is etiologically heterogeneous. Gene mutations on several different chromosomes are associated with familial inherited forms of Alzheimer's disease.

A major strategy for the treatment of Alzheimer's disease has focused on the relation between memory impairment and dysfunction of the acetylcholine neurotransmitter system. Other treatment strategies to delay or diminish the progression of Alzheimer's disease are being explored. Behavioral and pharmacological interventions are also available to treat the specific behavioral disturbances that can occur in Alzheimer's disease.

Alzheimer's disease

[′älts‚hī·mərz di‚zēz]
(medicine)
A progressive neurodegenerative disease characterized by loss of function and death of nerve cells in several areas of the brain, leading to loss of cognitive function such as memory and language; the most common cause of senile dementia. Abbreviated AD.

Alzheimer's disease

a disorder of the brain resulting in a progressive decline in intellectual and physical abilities and eventual dementia
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